3350-30-9Relevant academic research and scientific papers
Total synthesis, molecular editing and evaluation of a tripyrrolic natural product: The case of "butylcycloheptylprodigiosin"
Fuerstner, Alois,Radkowski, Karin,Peters, Hartwig,Seidel, Guenter,Wirtz, Conny,Mynott, Richard,Lehmann, Christian W.
, p. 1929 - 1945 (2007)
Conflicting reports are found in the literature on whether the ortho-pyrrolophane derivative 6, which has been named " butylcycloheptylprodigiosin" even though it is a cyclononane derivative, is a natural product or merely a mis-assigned structure. This dispute has now been resolved by an unambiguous total synthesis of this complex alkaloid which confirms the initial structure assignment. The chosen approach is largely catalysis-based, featuring the first application of a "Narasaka-Heck" reaction in natural product chemistry. This palladium-catalyzed transformation allows the unsaturated oxime ester 26 to be converted into the bicyclic dihydropyrrole 27. Other notable reactions of the reported approach to 6 are a regioselective Tsuji-Trost reaction of the doubly allylic acetate 21 with methyl acetoacetate. a base-induced aromatization of 27 to the corresponding pyrrole 28. a chemoselective oxidation of the benzylic methyl group in 33 with cerium ammonium nitrate in a biphasic reaction medium that does not affect the labile pyrrole nucleus, and a Suzuki cross-coupling for the completion of the heterocyclic domain. Diversification in the latter step leads to a set of analogues that differ from the natural product in the terminal (hetero)arene ring. This structural modification results in complete loss of the very pronounced ability of the parent compound 6 to induce oxidative cleavage in double stranded DNA in the presence of Cu11. Several cyclononane-, cyclononene- and cyclononadiene derivatives prepared en route to 6 have been characterized by crystal structure analysis, allowing the conformational behavior of nine-membered carbocycles to be studied.
Synthetic Entry to Polyfunctionalized Molecules through the [3+2]-Cycloaddition of Thiocarbonyl Ylides
Habiger, Christoph,Haut, Franz-Lucas,Korber, Johannes Nepomuk,Müller, Thomas,Magauer, Thomas,Mayer, Peter,Speck, Klaus,Wurst, Klaus
, (2019/09/06)
Here we present a comprehensive study on the [3+2]-cycloaddition of thiocarbonyl ylides with a wide variety of alkenes and alkynes. The obtained dihydro- and tetrahydrothiophene products serve as exceptionally versatile intermediates providing access to thiophenes, dienes, dendralenes, and vic-quarternary carbon centers. The use of high-pressure conditions enables thermally unstable, sterically encumbered or moderately reactive substrates to undergo the cycloaddition under mild conditions, thereby increasing the yield by up to 58percent. In addition, we showcase its utility by the formal syntheses of the pharmaceuticals NGB 4420 and tenilapine.
Synthesis of Cyclic Peptide Mimetics by the Successive Ring Expansion of Lactams
Stephens, Thomas C.,Lodi, Mahendar,Steer, Andrew M.,Lin, Yun,Gill, Matthew T.,Unsworth, William P.
, p. 13314 - 13318 (2017/10/05)
A successive ring-expansion protocol is reported that enables the controlled insertion of natural and non-natural amino acid fragments into lactams. Amino acids can be installed into macrocycles via an operationally simple and scalable iterative procedure, without the need for high dilution. This method is expected to be of broad utility, especially for the synthesis of medicinally important cyclic peptide mimetics.
Structure-reactivity relationship for alcohol oxidations via hydride transfer to a carbocationic oxidizing agent
Lu, Yun,Bradshaw, Joshua,Zhao, Yu,Kuester, William,Kabotso, Daniel
, p. 1172 - 1178 (2013/01/12)
Second-order rate constants were determined for the oxidation of 27 alcohols (R1R2CHOH) by a carbocationic oxidizing agent, 9-phenylxanthylium ion, in acetontrile at 60°C. Alcohols include open-chain alkyl, cycloalkyl, and unsaturated alcohols. Kinetic isotope effects for the reaction of 1-phenylethanol were determined at three H/D positions of the alcohol (KIEα-D=3.9, KIEβ-D3=1.03, KIE OD=1.10). These KIE results are consistent with those we previously reported for the 2-propanol reaction, suggesting that these reactions follow a hydride-proton sequential transfer mechanism that involves a rate-limiting formation of the α-hydroxy carbocation intermediate. Structure-reactivity relationship for alcohol oxidations was deeply discussed on the basis of the observed structural effects on the formation of the carbocationic transition state (Cδ+-OH). Efficiencies of alcohol oxidations are largely dependent upon the alcohol structures. Steric hindrance effect and ring strain relief effect win over the electronic effect in determining the rates of the oxidations of open-chain alkyl and cycloalkyl alcohols. Unhindered secondary alkyl alcohols would be selectively oxidized in the presence of primary and hindered secondary alkyl alcohols. Strained C7-C11 cycloalkyl alcohols react faster than cyclohexyl alcohol, whereas the strained C5 and C12 alcohols react slower. Aromatic alcohols would be efficiently and selectively oxidized in the presence of aliphatic alcohols of comparable steric requirements. This structure-reactivity relationship for alcohol oxidations via hydride-transfer mechanism is hoped to provide a useful guidance for the selective oxidation of certain alcohol functional groups in organic synthesis. Copyright
Oxidation catalytic system and oxidation process using the same
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, (2008/06/13)
A substrate (e.g., a cycloalkane, a polycyclic hydrocarbon, an aromatic compound having a methyl group or methylene group adjacent to an aromatic ring) is oxidized with oxygen in the presence of an oxidation catalyst comprising an imide compound of the following formula (1) (e.g., N-hydroxyphthalimide), and a co-catalyst (except phosphovanadomolybdic acid) containing an element selected from the group consisting of Group 2A elements of the Periodic Table of Elements, transition metals (Group 3A to 7A elements, Group 8 elements, Group 1B elements and Group 2B elements of the Periodic Table of Elements) and Group 3B elements of the Periodic Table of Elements, for the formation of an oxide (e.g., a ketone, an alcohol, a carboxylic acid): STR1 wherein R1 and R2 represent a substituent such as a hydrogen atom or a halogen atom, or R1 and R2 may together form a double bond or an aromatic or nonaromatic 5- to 12-membered ring, X is O or OH, and n is 1 to 3.
Cascade rearrangement of spiroepoxymethyl radicals into 2-oxocycloalkyl radicals: Evaluation of a two-carbon cycloalkanone ring expansion
Afzal, Mohammad,Walton, John C.
, p. 937 - 945 (2007/10/03)
Series of 2-bromomethyl- and 2-hydroxymethyl-1-oxaspiro[2.n]alkanes were prepared from cycloalkanones by initial Wadsworth-Horner-Emmons methodology to afford ester-substituted methylenecycloalkanes. The latter were selectively reduced to hydroxymethylmethylenecycloalkanes which were epoxidised with peroxyacetic acid. Homolytic reactions were studied by EPR spectroscopy which enabled transient 3-oxoalk-1-enyl radicals, and their cyclisation products, 2-oxocycloalkyl and 2-oxocycloalkylmethyl radicals, to be characterised. This evidence, together with end product analyses of organotin hydride reductions of the 2-bromomethyl-1-oxaspiro[2.n]alkanes, established that the initial spiroepoxymethyl radicals rearranged by a three-stage cascade of two consecutive β-scissions followed by a cyclisation. Cyclisations of the 3-oxoalk-1-enyl radicals took place mainly in the endo-mode to afford 2-oxocycloalkyl radicals, except for the 5-oxohept-6-enyl radical for which exo-cyclisation to generate the 2-oxocyclohexylmethyl radical was preferred. Kinetic data for the exo-and endo-cyclisations of the 4-oxohex-5-enyl radical were obtained from tributyltin hydride mediated reactions of 2-bromomethyl-1-oxaspiro[2.3]hexane.
Preparation, Properties, and Reactions of Metal-Containing Heterocycles, XCVI. Mono-, Di- and Trinuclear Metallacycloalkanes of the Iron-Triad
Lindner, Ekkehard,Leibfritz, Thomas,Fawzi, Riad,Steimann, Manfred
, p. 347 - 356 (2007/10/03)
The reaction of the bis(triflates) with Na2 in dimethyl ether affords the osmacycloalkanes 2a, 2b and 2f-i (m = 5, 6, 10, 12, 14, 16), diosmacycloalkanes 3a-i (m = 5-10, 12, 14, 16), and triosmacycloalkanes 4a-i (m = 5-10, 12, 14, 16).The structure of 3f was investigated by an X-ray structural analysis.This 22-membered diosmacycle crystallizes in the space group P1/ with Z = 1.If the unsaturated cis-4-octen-1,8-diyl bis(trifluoromethanesulfonate) (5) is treated with Na2 the diosmacyclooctadeca-5,14- diene 6 is obtained.By treating the bis(triflates) 1a, d with Na2 the corresponding ferracycloalkanes are formed only in situ.Insertion of carbon monoxide into the M-C ? bonds leads to the cyclic ketones 7a, d and to the diketone 8d. - Keywords: Metallacycloalkanes; Metallacycloalkenes; Osmium; Iron; Cyclic ketones; Metallacycles
Photoinduced Molecular Transformations. Part 155. General Synthesis of Macrocyclic Ketones based on a Ring Expansion involving a Selective β-Scission of Alkoxyl Radicals, its Applications to a New Synthesis of (+/-)-Isocaryophyllene and (+/-)-Caryophyllene, and a Conformational Analy...
Suginome, Hiroshi,Kondoh, Takahiko,Gogonea, Camelia,Singh, Vishwakarma,Goto, Hitoshi,Osawa, Eiji
, p. 69 - 82 (2007/10/02)
The method used for a general synthesis of macrocyclic ketones based on a ring expansion involving a selective β-scission of alkoxyl radicals devised by Suginome and Yamada was extended and modified.Thus, cycloalkanones were transformed into the corresponding α-(ω-iodoalkyl)-cycloalkanones by alkylation of the corresponding lithium enolates with either 1,3-diiodopropane or 1,4-diiodobutane.Treatment of these α-iodoalkyl cyclic ketones with samarium iodide gave bicyclic tertiary alcohols.The generation of the alkoxyl radicals from the bicyclic alcohols by irradiation of the corresponding hypoiodites generated with mercury(II) oxide - iodine - pyridine in benzene resulted in a selective β-scission of their ring-junction bond to give high yields of macrocyclic ketones carrying an iodine which can be removed with tributyltin hydride.The method was then applied to new syntheses of (+/-)-isocaryophyllene and (+/-)-caryophyllene.Thus, ω-iodopropylation of ethyl 7,7-dimethyl-2-oxobicyclooctane-3-carboxylate, followed by cyclization of the resulting α-(ω-iodoalkyl)cycloalkanone with samarium diiodide, gave cis-transoid-cis-ethyl 1-hydroxy-4,4-dimethyltricyclo2,5>undecane-8-carboxylate (69percent).The ethoxycarbonyl group of this tricyclic alcohol was transformed into a methyl group by the standard method.Irradiation of a solution of the hypoiodite, prepared by the method mentioned above, with Pyrex-filtered light gave the corresponding cis-bicycloundecenone (15percent), its exomethylene isomer (2,5>undecan-1-ol mentioned above were correlated with the three products.
1-Alkenylcycloalkoxy Radical Chemistry. A Two-Carbon Ring Expansion Methodology
Galatsis, Paul,Millan, Scott D.,Faber, Tim
, p. 1215 - 1220 (2007/10/02)
The exploitation of alkoxy radicals derived from 1-ethenylcycloalkanols for use in a two-carbon ring expansion protocol was proposed.Direct one-pot alkoxy radical-mediated fragmentation-cyclization was not feasible since the reactive intermediate was quenched by iodine in the reaction mixture.However, via the use of iodo epoxides 3, the tandem fragmentation-cyclization sequence could be accomplished.This afforded ring-expanded products via an endo mode of cyclization, although in one example product from an exo mode of cyclization was also isolated.This methodologywas shown to be valid for large ring compounds as well.The intermediary of iodo epoxides 3 also afforded improved yields as compared to the direct cyclization of iodo enones 4.These results are the first examples of radical cyclization to medium-sized carbocycles.
Ring Enlargement of Boracyclanes via Sequential One-Carbon Homologation. The First Synthesis of Boracyclanes in the Strained Medium Ring Range.
Brown, Herbert C.,Phadke, Avinash S.,Rangaishenvi, Milind V.
, p. 6263 - 6264 (2007/10/02)
We explored the Matteson homologation procedure as a means of enlarging the size of the ring in B-methoxyboracyclanes.
